Effect of induced airway inflammation in asthma : the expression of trefoil factors, secretoglobins and genes involved in histone acetylation

Asthma is an incapacitating disease of the respiratory system, which causes extensive morbidity and mortality worldwide. Asthma affects more than 300 million people globally(Masoli et al. 2004). In Australia, it affects 10.2% of the population (Masoli et al. 2004) and causes 60,000 people to be hospitalised annually. Health care expenditure due to asthma in Australia was $606 million in 2004–2005. There are four primary biological factors that function in the initiation and exacerbation of asthma. Airway inflammation is important as it is often the first response to an airway insult, initiating the three other components: bronchoconstriction, mucus hyper-secretion and hyper-reactivity. The mediators involved in asthma are still not well understood, and current anti-inflammatory corticosteroid treatments are not effective with all asthmatics. As there is currently no cure for asthma, and airway inflammation is the primary component of the disease, it is important that we understand and investigate the mediators of airway inflammation to look for a potential cure and to produce better therapeutics to treat the inflammation. Trefoil factors (TFFs) and secretoglobins (SCGBs) are small secreted proteins involved in the mediation of inflammation and epithelial restitution. TFFs are pro-inflammatory and SCGBs anti-inflammatory by nature. The hypothesis of this study is that in response to induced acute airway inflammation, the expression of TFF1 and TFF3 will increase and expression of SCGB1A1 and SCGB3A2 will decrease in non-asthmatics (N-A), asthmatics medicating with bronchodilators (A-BD) and asthmatics medicating with corticosteroids (A-ST). When comparing the three groups, we expect to see higher expression of the TFFs in the A-BD group compared to the N-A and A-ST groups, indicating that inflammation is mediated by TFFs in asthma and that corticosteroid medication controls their expression as part of the control of inflammation. We expect to see the opposite with SCGBs, with a greater decrease in the A-BD group compared to the other two groups, suggesting that the A-BD group has the least anti-inflammatory activity in response to inflammatory insult. Epigenetic modification plays a role in the regulation of genes that initiate disease states such as inflammatory conditions and cancers. Histone acetylation is one such modification, which involves the acetylation of histones in chromatin by histone acetyltransferases (HATs). This increases the transcription of genes involved with inflammation or enrols histone deacetylases (HDACs) to down-regulate the transcription of inflammatory genes. These HATs and HDACs work in a homeostatic fashion; however, in the event of inflammation, increased HAT activity can stimulate further inflammation, which is believed to be the mechanism involved in some inflammatory diseases. This study hypothesises that in response to inflammation, the expression of HDACs (HDAC1-5) will decrease and the expression of HATs (NCOA1-3, HAT-1 and CREBBP) will increase in all groups. When comparing the expression between the groups, it was expected that a greater decrease in HDACs and a greater increase in HATs will be seen in the A-BD group compared to the other two groups. This would identify histone acetylation as a mechanism involved in the inflammatory condition of asthma and indicate that corticosteroids may treat the inflammation in asthma at least in part by controlling histone acetylation. The aim of the project was to compare the expression of inflammatory genes TFF1, TFF3, SCGB1A1 and SCGB3A2, as well as to compare the gene expression of HDAC1-5, NCOA1-3, HAT-1 and CREBBP within and between N-A (n=15), A-BD (n=15) and A-ST (n=15) groups in response to inflammation. This was performed by collecting airway cells and proteins by sputum induction in three sessions. The sessions were coordinated into an initial baseline collection (SI-1), followed by a second session at least one week later (SI-2) and a third session, six hours after SI-2 to collect a sample containing the resultant acute inflammation caused in SI-2 (SI-3). Analysis of the SI-1 and SI-2 samples in all three groups had high amounts of variability between samples. The samples were taken at least one weak apart and the environmental stimuli on each participant outside of the testing sessions could not be controlled. For this reason, the SI-1 samples were not used for analysis; instead SI-2 and SI-3 samples were compared as they were same-day collections, reducing the probability of differences being due to anything other than the sputum induction. The gene expressions of the TFFs, SCGBs, HDACs and HATs were analysed using real-time PCR. Western blot analysis was performed to analyse the protein concentrations of the TFFs and SCGBs in secreted fractions of the sputum collection. Both the secreted and intracellular protein fractions collected from the sputum inductions for pre- and post-inflammation (SI-2, SI-3) samples of the N-A and A-BD groups were analysed using a proteomic method called iTRAQ. This allowed the comparison of the change in protein expression as a result of airway inflammation in each group. This technique was used as a discovery method to identify novel proteins that are modulated by induced acute airway inflammation. Any proteins of interest would then be further validated and used for future research. Inflammation was achieved in the SI-3 samples of the N-A group with a 21% unit increase in % neutrophils compared to SI-2 (p=0.01). The N-A group had a marked 5.5-fold decrease in HDAC1 gene expression in SI-3 compared to SI-2 (p=0.03). No differences were seen in any of the TFFs, SCGBs or any of the rest of the HDACs and HATs. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. However, non-significant analysis of the data displayed increases in TFF1 and TFF3, and decreases in SCGB1A1 and SCGB3A2 for the majority of SI-3 samples compared to SI-2. The A-BD group also presented a marked increase in neutrophils in the SI-3 samples compared to SI-2 (27% unit increase, p=0.04). The A-BD group had a significant increase in TFF3 and SCGB1A1 gene expression concomitant with induced acute airway inflammation. A 7.3-fold increase in TFF3 (p=0.05) in SI-3 indicated that TFF3 is linked to inflammation in asthmatics. A 2.8-fold increase in SCGB1A1 (p=0.03) indicated that this gene is also up-regulated, suggesting that this SCGB is expressed to try to combat induced acute airway inflammation. No significant changes were seen in any of the other genes analysed. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. However, non-significant analysis of the data displayed an increase in TFF1 and TFF3, and a decrease in SCGB1A1 and SCGB3A2 in SI-3, similar to that seen in the N-A group. The A-ST group was different from the A-BD group, characterised by the use of inhaled corticosteroid medication to treat asthma symptoms. Inhaled corticosteroids are known to treat asthma symptoms through the control of inflammation. Therefore, it was expected that corticosteroid medication would also control the expression of TFFs, SCGBs, HATs and HDACs. Gene expression results only identified a 7.6-fold decrease in HDAC2 expression in SI-3 (p=0.001), which is proposed to be due to the up-regulation of HDAC2 protein that is known to be a function of corticosteroid use. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. The gene expression in SI-2 and SI-3 in each group was compared. When comparing the A-BD group to the N-A group, a 9-fold increase in TFF3 (p=0.008) and a 34-fold increase in SCGB1A1 (p=0.03) were seen in the SI-3 samples. Comparisons of the A-ST group to the N-A group had an increased expression in SI-2 samples for HDAC5 (3.6-fold, p=0.04), NCOA2 (8.5-fold, p=0.04), NCOA3 (17-fold, p=0.01), HAT-1 (36-fold, p=0.003) and CREBBP (13-fold, p=0.001). The SI-3 samples in the A-ST group compared to the N-A group had increased expression for HDAC1 (6.4-fold, p=0.04), HDAC5 (5.2-fold, p=0.008), NCOA2 (9.6-fold, p=0.03), NCOA3 (16-fold, p=0.06), HAT-1 (41-fold, p<0.001) and CREBBP (31-fold, p=0.001). Comparisons of the A-ST group to the A-BD group had SI-2 increases in HDAC1 (3.8-fold, p=0.03), NCOA3 (4.5-fold, p=0.03), HAT-1 (5.3-fold, p=0.01) and CREBBP (23-fold, p=0.001), while SI-3 comparisons saw a decrease in HDAC2 (41-fold, p=0.008) and increases in HAT-1 (4.3-fold, p=0.003) and CREBBP (40-fold, p=0.001). Results showed that TFF3 and SCGB1A1 expression is higher in asthmatics than non-asthmatics and that histone acetylation is more active in the A-ST group than either the N-A or A-BD group, which suggests that histone acetylation activity may be positively correlated with asthma severity. The iTRAQ proteomic analysis of the secreted protein samples identified the SCGB1A1 protein and found it to be decreased in both the N-A and A-BD groups post-inflammation, but significantly so only in the A-BD group. Although no significant results were obtained from the western blot data, both groups displayed a decrease in SCGB1A1 concentration in SI-3 samples, suggesting a correlation with the proteomic data. Only 31 peptides were identified from the secreted samples. The intracellular iTRAQ analysis successfully identified 664 peptides, eight of which had differential expression in association with induced acute airway inflammation. Significant increases were seen in the A-BD group in SI-3 compared to SI-2 than in the N-A group in chloride intracellular channel protein 1, keratin-19, eosinophil cationic protein, calnexin, peroxiredoxin-5, and ATP-synthase delta subunit, while decreases were seen in cystatin-A and mucin-5AC. The iTRAQ analysis was only a discovery measure and further validation must be performed. In summary, the expression of TFFs and SCGBs differed between non-asthmatics and asthmatics. It is clear that TFF3 is active in the airway inflammation associated with asthma as indicated by an increase associated with inflammation in the A-BD group compared to the N-A group. Results for HDAC and HAT genes showed high HAT expression in the A-ST group compared to the N-A and A-BD groups, suggesting that histone acetyltransferases may be responsible for the characteristic unregulated inflammatory symptoms of asthmatics taking corticosteroids. Interestingly, corticosteroid medication did not seem to silence the expression of the analysed HAT genes, which indicates that corticosteroids may not control inflammation by direct regulation of HATs, but instead by competition, most probably with HDAC2 protein. As a discovery tool, iTRAQ is a potent method to both identify and compare the concentration of proteins between samples. The method is a powerful first step into the identification of novel proteins that are regulated in response to different treatments.

Second international workshop on theory and applications of process visualization

The representation of business process models has been a continuing research topic for many years now. However, many process model representations have not developed beyond minimally interactive 2D icon-based representations of directed graphs and networks, with little or no annotation for information overlays. In addition, very few of these representations have undergone a thorough analysis or design process with reference to psychological theories on data and process visualization. This dearth of visualization research, we believe, has led to problems with BPM uptake in some organizations, as the representations can be difficult for stakeholders to understand, and thus remains an open research question for the BPM community. In addition, business analysts and process modeling experts themselves need visual representations that are able to assist with key BPM life cycle tasks in the process of generating optimal solutions. With the rise of desktop computers and commodity mobile devices capable of supporting rich interactive 3D environments, we believe that much of the research performed in computer human interaction, virtual reality, games and interactive entertainment have much potential in areas of BPM; to engage, provide insight, and to promote collaboration amongst analysts and stakeholders alike. We believe this is a timely topic, with research emerging in a number of places around the globe, relevant to this workshop. This is the second TAProViz workshop being run at BPM. The intention this year is to consolidate on the results of last year's successful workshop by further developing this important topic, identifying the key research topics of interest to the BPM visualization community.

Characterisation of candidate nuclear genes for species delineation in the genus Cherax

Understanding the evolutionary history and phylogenetic relationships between rare and common species is necessary for the effective management of rare species. The genus Cherax, a group of freshwater crayfish species, is of interest in this regard as a number of species are rare or have restricted distributions while other species are common and widespread. Here we describe the characterisation of three novel nuclear genes of the haemocyanin superfamily for phylogenetic reconstruction of the genus. All novel markers developed in this study amplified consistently in species from three divergent clades of the genus Cherax. The level of polymorphism found in these markers was consistently higher than that found in other nuclear genes previously used in invertebrate systematics, such as NaK ATP-ase. In combination, these markers will be useful to delineate phylogenetic relationships between rare and common Cherax species.

The employment effects of gender discrimination in Australia 1994-95

Interpreting the unexplained component of the gender wage gap as indicative of discrimination, the empirical literature to date has tended to ignore the potential impact wage discrimination may have on employment. Clearly, employment effects will arise if discrimination lowers the female offered wage and the labour supply curve is upward sloping. The empirical analysis employs the ABS Income Distribution Survey 1994–95 and finds evidence of both wage and associated employment effects. The analysis is replicated for the earlier period 1989–90. A comparison across time is of interest given the substantial deregulation of the Australian labour market over the period.

Investigation of the NOTCH3 and TNFSF7 genes on C19p13 as candidates for migraine

To investigate the migraine locus around the C19p13 region through analysis of the NOTCH3 gene (C19p13.2-p13.1), previously shown to be a gene involved in CADASIL and the TNFSF7 gene (C19p13), homologous to the ligands of TNF-alpha and TNF-beta, genes that have previously been associated with migraine. The NOTCH3 gene was analysed by sequencing all exons with known CADASIL mutations in a typical (non-familial hemiplegic) migraine family (MF1) that has previously been shown to be linked to C19p13. The TNFSF7 gene was investigated through SNP association analysis using a matched case-control migraine population. NOTCH3 gene sequencing results for affected members of MF1 proved to be negative for all known sequence variants giving rise to mutations for CADASIL. TNFSF7 gene chi-square results showed non-significant P values across all populations tested against controls, except for the MO subgroup which displayed a possible association with the TNFSF7 SNP (genotype, allele analysis P = 0.036, P = 0.017 respectively). Our results suggest that common migraine is not caused by any known CADASIL mutations in the NOTCH3 gene of interest. However, the TNFSF7 gene displayed signs of involvement in a MO affected population and indicates that further independent studies of this marker are warranted.

A portrayal of new entrants into the Australian economy (Entrepreneurial individuals and ventures)

This paper provides a descriptive overview of the venture creation in Australia, those who participate in it and the types of firms they build. Findings of interest in this paper include: • The majority of business founders (89 per cent) state the motivation to start a new business is opportunity-driven rather than necessity driven. • The extent of under-representation of women business founders in Australia appears to be lower than international comparisons and has decreased over time. • Australian business founders tend to possess significant ‘human capital’ many are university-educated, and large shares have different types of experience that may benefit the start-up. • The major industries for start-up activities are Retailing; various service industries (Business Consulting; Health, Education and Social; other Consumer services); Construction, Manufacturing, and Agriculture. • A large proportion of CAUSEE respondents (49 per cent nascent firms and 46 per cent young firms) are members of start-up teams, which is similar to international comparisons.

Transitions in taste in Vietnam and the diaspora

This paper argues that food and styles of eating have become the predominant markers of social change for the Vietnamese in both Vietnam and in the diaspora. In post-socialist Vietnam the transition to a market economy has allowed for a huge growth in the number of restaurants and cafes, and in the north, a return to an earlier style of cooking. The intense interest and emphasis on food as embodied pleasure has meant that it has come to stand for the transition away from a heavily state-controlled economy. The new configurations of family and friendship are being framed by newly available ways of ‘eating out’, which are both a means of social display and distinction as well as an indicator of the tensions between reform and festivity within an authoritarian nation-state struggling to define itself in a globalising world. At the same time as food in Vietnam is undergoing rapid transformation so too has the Vietnamese diaspora enerationally changed its eating patterns. Although there as been a focus in the literature on food in the diaspora that emphasises the nostalgic and recuperative elements of ‘migrant food’, I argue that food is the prime mechanism of intercultural engagement for each diasporic generation. For older Vietnamese, Vietnamese restaurants and barbecues have been the sites of interplay between cultural tradition’ and innovation, and between Australianness and Vietnameseness, and these interstitial places continue to be important for younger Vietnamese. Within this established framework of cross-cultural interaction, for Vietnamese youth, the social settings of ‘ethnic food’, eaten at home and shared with family, have been grafted onto a sociality of eating fast food. This melding together of both invention and convention, of transgression and ordinariness provides the background against which young people from migrant backgrounds are reinvigorating the social spaces of food consumption and in the process both e-enchanting and destabilising the notion of migrant food.

What it means to be green : an examination of early stage environmental and sustainability focused firms

This paper examines ‘green’ entrepreneurial nascent and young firms in Australia. Findings of interest in this paper include: • Green entrepreneurs are more likely to be highly educated and have an extended depth of experience within their industry and are more likely to have started a business prior to their current venture. • Green entrepreneurs exhibit increased levels of innovation, with an increased focus on new & high technology, R&D and the development of proprietary technology. • Green entrepreneurs are most likely to be based upon a product rather than a service and have a higher emphasis upon growth when compared with non-green entrepreneurs. • Green entrepreneurial firms tend to have a longer venture creation process and draw financial resources from a larger number of sources and rely more upon equity as a means of financing their venture.

Capturing gazelles : features of high potential firms and new venture growth

This paper investigates the characteristics of ventures which have the potential to reach high growth and compares this with ‘everyday’ new ventures. Findings of interest in this paper include: • HP firms are characterised by higher human capital, are more likely to have a team of founders, are more likely to be product based. • HP firms are more likely to achieve more extreme levels of growth (both positive and negative). • HP ventures that make a loss are more likely to do so early in the venture process. Those that do hold on show that there can higher levels of loss made later on in firm development. HP firms have higher resource needs, in terms of seeking external finance, but are no more likely to receive external finance than regular firms.

Empirical evaluation of public transport travel time variability

Although transit travel time variability is essential for understanding the deterioration of reliability, optimising transit schedule and route choice; it has not attracted enough attention from the literature. This paper proposes public transport-oriented definitions of travel time variability and explores the distributions of public transport travel time using the Transit Signal Priority data. First, definitions of public transport travel time variability are established by extending the common definitions of variability in the literature and by using route and services data of public transport vehicles. Second, the paper explores the distribution of public transport travel time. A new approach for analysing the distributions involving all transit vehicles as well as vehicles from a specific route is proposed. The Lognormal distribution is revealed as the descriptors for public transport travel time from the same route and service. The methods described in this study could be of interest for both traffic managers and transit operators for planning and managing the transit systems.

Faster than the speed of print : reconciling ‘big data’ social media analysis and academic scholarship

The promise of ‘big data’ has generated a significant deal of interest in the development of new approaches to research in the humanities and social sciences, as well as a range of important critical interventions which warn of an unquestioned rush to ‘big data’. Drawing on the experiences made in developing innovative ‘big data’ approaches to social media research, this paper examines some of the repercussions for the scholarly research and publication practices of those researchers who do pursue the path of ‘big data’–centric investigation in their work. As researchers import the tools and methods of highly quantitative, statistical analysis from the ‘hard’ sciences into computational, digital humanities research, must they also subscribe to the language and assumptions underlying such ‘scientificity’? If so, how does this affect the choices made in gathering, processing, analysing, and disseminating the outcomes of digital humanities research? In particular, is there a need to rethink the forms and formats of publishing scholarly work in order to enable the rigorous scrutiny and replicability of research outcomes?

The effectiveness of health education using the teach-back method on adherence and self-management in chronic disease: A systematic review protocol

Review question/objective What is the effect of using the teach-back method for health education to improve adherence to treatment regimen and self-management in chronic disease? Inclusion criteria Types of participants This review will consider all studies that include adult patients (aged 18 years and over) in any healthcare setting, either as inpatients (eg acute care, medical and surgical wards) or those who attend primary health care, family medical practice, general medical practice, clinics, outpatient departments, rehabilitation or community settings. Participants need to have been diagnosed as having one or more chronic diseases including heart failure, diabetes, cardiovascular disease, cancer, respiratory disease, asthma, chronic obstructive pulmonary disease, chronic kidney disease, arthritis, epilepsy or a mental health condition. Studies that include seriously ill patients, and/or those who have impairments in verbal communication and cognitive function will be excluded. Types of intervention This review will consider studies that investigate the use of the teach-back method alone or in combination with other supporting education, either in routine or research intervention education programs; regardless of how long the programs were and whether or not a follow-up was conducted. The intervention could be delivered by any healthcare professional. The comparator will be any health education for chronic disease that does not include the teach-back method. Types of outcomes Primary outcomes of interest are disease-specific knowledge, adherence, and self-management knowledge, behavior and skills measured using patient report, nursing observation or validated measurement scales. Secondary outcomes include knowledge retention, self-efficacy, hospital readmission, hospitalization, and quality of life, also measured using patient report, nursing observation, hospital records or validated measurement scales.

The Art of Freestyle

"This book is intended to be instructional, inspirational and of interest to both novice and expert alike. The assumption is made that to even begin to playboat the paddler will already be an intermdiate white water boater familiar with basic strokes and boating skills. For the interested non paddler a glossary of terms is included. Part One gives an overview of the sport and lays the foundations of understanding on which the rest of the book builds, as well as exploring safety issues and exploring key concepts. Part Two describes and coaches the moves which are divided into intermediate and advanced standard. Part Three looks at how to train in order to hone your physical and mental skills and be 'the best you can be'. Never before has so much freestyle, rodeo and playboating information from so many great boaters been gathered together in one place. In a world dominated by the biggest, the fastest, the loudest...the most big headed, this book makes a stand. Whilst of course covering all the latest moves, the authors have not been frightened to start right back at basic concepts. Technical ability is nothing without knowledge, without planning and without stamina. This book tells you the secrets. Freestyle is a thinking person's sport. The authors, the contributors and the book's publisher have an unrivalled breadth of knowledge in this field, so let this book do some of the thinking for you. The full colour format and the emphasis on personal training and coaching make for a particularly easy read. When planning my preparation or training before a competition, I always try to evaluate its potential benefits in terms of how many places it will have helped me move up in the final results. As a general rule in life, any time spent off the water should be viewed with suspicion! However, use this time constructively and absorb the information in this book and you will reap your own rewards. The Art of Freestyle is a book genuinely written by paddlers for paddlers. It is often a hard task to get top athletes to part with their preferred training or competition techniques, but this book is full of such 'Top Tips'. This is not a book written just by its authors, but by a wealth of accomplished paddlers. It is this subtle combination that keeps the reader in the real world...believing in a move, not just imagining it. This is the real world...believe you can do it."--Playak Website

Get real : the development, implementation and evaluation of an intervention for primary aged children with High Functioning Autism

Children with Autism Spectrum Disorder experience difficulty in communication and in understanding the social world which can have negative consequences for their relationships, in managing emotions, and generally dealing with the challenges of everyday life. This thesis examines the effectiveness of the Active and Reflective components of the Get REAL program through the assessment of the detailed coding of video-recorded observations and longitudinal quantitative analysis. The aim of Get REAL is to increase the social, emotional, and cognitive learning of children with High Functioning Autism (HFA). Get REAL is a group program designed specifically for use in inclusive primary school settings. The Get REAL program was designed in response to the mixed success of generalisation of learning to new contexts of existing social skills programs. The theoretical foundation of Get REAL is based upon pedagogical theory and learning theory to facilitate transfer of learning, combined with experiential, individualised, evaluative and organisational approaches. This thesis is by publication and consists of four refereed journal papers; 1 accepted for publication and 3 that are under review. Paper 1 describes the development and theoretical basis of the Get REAL program and provides detail of the program structure and learning cycle. The focus of Paper 1 reflects the first question of interest in the thesis which is about the extent to which learning derived from participation in the program can be generalised to other contexts. Participants are 16 children with HFA ranging in age from 8-13 years. Results provided support for the generalisability of learning from Get REAL to home and school evidenced by parent and teacher data collected pre and post participation in Get REAL. Following establishment of the generalisation of learning from Get REAL, Papers 2 and 3 focus on the Active and Reflective components of the program in order to examine how individual and group learning takes place. Participants (N = 12) in the program are video-taped during the Active and Reflective Sessions. Using identical coding protocols of video data, improvements in prosocial behaviour and diminishing of inappropriate behaviours were apparent with the exception of perspective taking. Data also revealed that 2 of the participants had atypical trajectories. An in-depth case study analysis was then conducted with these 2 participants in Paper 4. Data included reports from health care and education professionals within the school and externally (e.g., paediatrician) and identified the multi-faceted nature of care needed for children with comorbid diagnoses and extremely challenging family circumstances as a complex task to effect change. Results of this research support the effectiveness of the Get REAL program in promoting pro social behaviours such as improvements in engaging with others and emotional regulation, and in diminishing unwanted behaviours such as conduct problems. Further, the gains made by the participating children were found to be generalisable beyond Get REAL to home and other school settings. The research contained in the thesis adds to current knowledge about how learning can take place for children with HFA. Results show that an experiential learning framework with a focus on social cognition, together with explicit teaching, scaffolded with video feedback, are key ingredients for the generalisation of social learning to broader contexts.

The life course of Australian researchers : experiences of applying for research funding

The life course of Australian researchers includes regular funding applications, which incur large personal and time costs. We previously estimated that Australian researchers spent 550 years preparing 3,727 proposals for the 2012 NHMRC Project Grant funding round, at an estimated annual salary cost of AU$66 million. Despite the worldwide importance of funding rounds, there is little evidence on what researchers think of the application process. We conducted a web-based survey of Australian researchers (May–July 2013) asking about their experience with NHMRC Project Grants. Almost all researchers (n=224 at 31 May) supported changes to the application (96%) and peer-review (88%) processes; 73% supported the introduction of shorter initial Expressions of Interest; and half (50%) provided extensive comments on the NHMRC processes. Researchers agreed preparing their proposals always took top priority over other work (97%) and personal (87%) commitments. More than half (57%) provided extensive comments on the ongoing personal impact of concurrent grant-writing and holiday seasons on family, children and other relationships. Researchers with experience on Grant Review Panels (34%) or as External Reviewers (78%) reported many sections of the proposals were rarely or never read, which suggests these sections could be cut with no impact on the quality of peer review. Our findings provide evidence on the experience of Australian researchers as applicants. The process of preparing, submitting and reviewing proposals could be streamlined to minimise the burden on applicants and peer reviewers, giving Australian researchers more time to work on actual research and be with their families.